1. Field of the Invention
The present invention relates to a new synthesis for aspartame, i.e., L-.alpha.aspartyl-L-phenylalanine methyl ester.
2. Description of Prior Art
Aspartame has sweetening properties similar to cane and beet sugar, and is used as a sweetening agent for foods and beverages, see for instance, U.S. Pat. No. 3,492,131.
Aspartame is a dipeptide, and, as such, is formed with an amide bond between an activated carboxyl group of the amino acid and the amino group of another amino acid. Activation is necessary to increase the rate and the yield of the condensation. In carrying out the formation process, the desired pure peptide requires the protection of all other functional groups not involved in the peptide bond formation, which means that after formation, the protecting groups must be removed. For instance, aspartame is known to be prepared by the reaction of an N-protected-L-aspartic anhydride with an L-phenylalanine methyl ester to yield a mixture of L-.alpha.-aspartyl-L-phenylalanine methyl ester and L-.beta.-aspartyl-L-phenylalanine methyl ester. The N-protecting groups used are the common N-protecting groups in peptide chemistry, for example benzyloxycarbonyl or a formyl group. N-deprotection is then carried out in presence of strong acids (U.S. Pat. No. 4,071,511). or in the presence of hydroxylamine (U.S. Pat. No. 4,021,418). Neither of these methods are entirely suitable for industrial purposes, however. Deformylation results in low yields, requires expensive reagents, and often results in esterification of the .beta.-carboxy group, or hydrolysis of the ester or peptide bond. Moreover, the above process requires the further step of separating the .alpha.- and .beta.-isomers (the .beta.-isomer does not have sweetening properties), which leads to a cost increase.
It would be desirable to provide for an industrial process for the production of aspartame wherein the deformylation will occur with such selectivity that side reactions such as hydrolysis of the ester or of the peptide bond is minimized.